Pub Date : 2025-11-10DOI: 10.1016/j.mehy.2025.111815
Flávio Furtado de Farias , Marcelo Coertjens
Why does the human body preferentially oxidize lipids over glucose at rest? Moving beyond energy-efficiency models, we propose an evolutionary explanation: this configuration may be an adaptation to minimize irreversible molecular damage from protein glycation. The Safe Dissipation Hypothesis (SDH) posits that basal lipid oxidation limits the accumulation of advanced glycation end-products (AGEs), which degrade slow-turnover proteins like collagen and crystallins. Metabolic evolution thus favored phenotypes that suppress unnecessary glycolytic flux, even at the cost of submaximal ATP yield. Supporting mechanisms include hepatic glucose buffering, upregulation of pyruvate dehydrogenase kinase 4 (PDK4), and enzymatic defenses like glyoxalase-1 (GLO1). We hypothesize that this architecture—shaped by ancestral intermittent food availability—underlies the metabolic mismatch behind modern hyperglycemia-related diseases. Predictions include lower collagen-AGEs in pre-agricultural remains and population-specific genetic signatures in pathways like GLO1 and PDK4. The SDH reframes aging and chronic disease as consequences of disrupted anti-glycation dynamics, intrinsically linking fuel preference to molecular preservation and longevity.
{"title":"Safe dissipation hypothesis: glycation as an evolutionary force shaping human metabolism","authors":"Flávio Furtado de Farias , Marcelo Coertjens","doi":"10.1016/j.mehy.2025.111815","DOIUrl":"10.1016/j.mehy.2025.111815","url":null,"abstract":"<div><div>Why does the human body preferentially oxidize lipids over glucose at rest? Moving beyond energy-efficiency models, we propose an evolutionary explanation: this configuration may be an adaptation to minimize irreversible molecular damage from protein glycation. The Safe Dissipation Hypothesis (SDH) posits that basal lipid oxidation limits the accumulation of advanced glycation end-products (AGEs), which degrade slow-turnover proteins like collagen and crystallins. Metabolic evolution thus favored phenotypes that suppress unnecessary glycolytic flux, even at the cost of submaximal ATP yield. Supporting mechanisms include hepatic glucose buffering, upregulation of pyruvate dehydrogenase kinase 4 (PDK4), and enzymatic defenses like glyoxalase-1 (GLO1). We hypothesize that this architecture—shaped by ancestral intermittent food availability—underlies the metabolic mismatch behind modern hyperglycemia-related diseases. Predictions include lower collagen-AGEs in pre-agricultural remains and population-specific genetic signatures in pathways like GLO1 and PDK4. The SDH reframes aging and chronic disease as consequences of disrupted anti-glycation dynamics, intrinsically linking fuel preference to molecular preservation and longevity.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111815"},"PeriodicalIF":0.8,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-09DOI: 10.1016/j.mehy.2025.111813
Zhe-Ying Jiang , Zi-Qi Zhu , Ying Wang , Wei-Jia Meng , Cui-Ping Li , Lian-Ping He , Xiang-Hu Wang
Lipid metabolism is crucial for cellular function and overall health. Dysregulation of lipid metabolism is associated with a variety of diseases, including obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases. Studies have shown that the gut microbiota can regulate the synthesis and transformation of bile acids, including Lithocholic acid (LCA). participates in the regulation of glucose, lipid, and drug metabolism by interacting with a variety of nuclear receptors, such as farnesoid X receptor, G-protein-coupled bile acid receptor, Vitamin D receptor, and pregnane X receptor. Recently, it has been discovered that regulating bile acid metabolism through LCA may provide a new strategy for managing lipid metabolism dysregulation. Excessive dietary iron has been proven to significantly affect the composition and diversity of the gut microbiota. Therefore, we hypothesize that dietary iron may indirectly affect lipid metabolism by influencing intestinal LCA levels.
{"title":"Excess iron in food could indirectly affect lipid metabolism by affecting intestinal lithocholic acid levels: A scientific hypothesis","authors":"Zhe-Ying Jiang , Zi-Qi Zhu , Ying Wang , Wei-Jia Meng , Cui-Ping Li , Lian-Ping He , Xiang-Hu Wang","doi":"10.1016/j.mehy.2025.111813","DOIUrl":"10.1016/j.mehy.2025.111813","url":null,"abstract":"<div><div>Lipid metabolism is crucial for cellular function and overall health. Dysregulation of lipid metabolism is associated with a variety of diseases, including obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases. Studies have shown that the gut microbiota can regulate the synthesis and transformation of bile acids, including Lithocholic acid (LCA). participates in the regulation of glucose, lipid, and drug metabolism by interacting with a variety of nuclear receptors, such as farnesoid X receptor, G-protein-coupled bile acid receptor, Vitamin D receptor, and pregnane X receptor. Recently, it has been discovered that regulating bile acid metabolism through LCA may provide a new strategy for managing lipid metabolism dysregulation. Excessive dietary iron has been proven to significantly affect the composition and diversity of the gut microbiota. Therefore, we hypothesize that dietary iron may indirectly affect lipid metabolism by influencing intestinal LCA levels.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111813"},"PeriodicalIF":0.8,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.mehy.2025.111808
Fernanda Moura Vargas Dias , Carolina Fiorin Anhoque , Christian Nogueira de Barros , Renata Goltara Liboni Vescovi , Fernando Zanela da Silva Arêas
Migraine is a prevalent neurovascular disorder marked by cortical hyperexcitability, trigeminovascular activation, and central sensitization. While pharmacological therapies are available, many patients exhibit partial responses or intolerable side effects. We hypothesize that combining repetitive transcranial magnetic stimulation (rTMS) with mindfulness-based interventions (MBIs) may offer a synergistic, non-pharmacological approach to migraine management. rTMS, particularly when applied over the dorsolateral prefrontal cortex (DLPFC), has shown promise in modulating cortical excitability and reducing migraine frequency. Concurrently, mindfulness practices have demonstrated neurophysiological effects—including enhanced frontal cortical inhibition, increased alpha wave activity, and reduced limbic reactivity—that parallel rTMS-induced changes. Both interventions influence key regions implicated in pain perception and emotional regulation, suggesting overlapping mechanisms. We propose that mindfulness may act as a neurocognitive enhancer of rTMS-induced plasticity, while rTMS may acutely normalize dysfunctional cortical dynamics, facilitating a deeper engagement in mindfulness practice. This dual modulation could target both the physiological and psychological components of migraine, producing sustained therapeutic effects. Preliminary clinical data in other populations support greater efficacy when rTMS and mindfulness are combined, though this has not yet been systematically explored in migraine. We call for mechanistically informed, controlled studies to evaluate this hypothesis and to define optimal timing, dosing, and patient selection criteria. If validated, this integrative model may represent a novel treatment paradigm for individuals with refractory migraine.
{"title":"Enhancing the effects of mindfulness in migraine patients through transcranial magnetic stimulation: A plausible hypothesis","authors":"Fernanda Moura Vargas Dias , Carolina Fiorin Anhoque , Christian Nogueira de Barros , Renata Goltara Liboni Vescovi , Fernando Zanela da Silva Arêas","doi":"10.1016/j.mehy.2025.111808","DOIUrl":"10.1016/j.mehy.2025.111808","url":null,"abstract":"<div><div>Migraine is a prevalent neurovascular disorder marked by cortical hyperexcitability, trigeminovascular activation, and central sensitization. While pharmacological therapies are available, many patients exhibit partial responses or intolerable side effects. We hypothesize that combining repetitive transcranial magnetic stimulation (rTMS) with mindfulness-based interventions (MBIs) may offer a synergistic, non-pharmacological approach to migraine management. rTMS, particularly when applied over the dorsolateral prefrontal cortex (DLPFC), has shown promise in modulating cortical excitability and reducing migraine frequency. Concurrently, mindfulness practices have demonstrated neurophysiological effects—including enhanced frontal cortical inhibition, increased alpha wave activity, and reduced limbic reactivity—that parallel rTMS-induced changes. Both interventions influence key regions implicated in pain perception and emotional regulation, suggesting overlapping mechanisms. We propose that mindfulness may act as a neurocognitive enhancer of rTMS-induced plasticity, while rTMS may acutely normalize dysfunctional cortical dynamics, facilitating a deeper engagement in mindfulness practice. This dual modulation could target both the physiological and psychological components of migraine, producing sustained therapeutic effects. Preliminary clinical data in other populations support greater efficacy when rTMS and mindfulness are combined, though this has not yet been systematically explored in migraine. We call for mechanistically informed, controlled studies to evaluate this hypothesis and to define optimal timing, dosing, and patient selection criteria. If validated, this integrative model may represent a novel treatment paradigm for individuals with refractory migraine.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111808"},"PeriodicalIF":0.8,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.mehy.2025.111809
Ofer N. Gofrit , Tzahi Neuman
An ecotone is a concept in ecology that refers to a transition zone between two biomes such as forest–grassland. The exposure to environmental gradients induces physiological stress on bordering biotas leading to high genetic diversity, high mutation rate, and intensified selection pressures. We hypothesized that similar forces act on interfaces between epithelia, that these transitions zones can be viewed as ecotones, and that cancer develops in these sites. Examples are: carcinoma of the larynx most commonly developing in the ecotone between the squamous stratified epithelium of the upper glottis and the pseudo-stratified epithelium of the lower glottis, esophageal adenocarcinoma develops in the ecotone between the stratified squamous epithelium of the esophagus and the simple columnar stomach epithelium, anal cancer develops at the ecotone between the squamous stratified epithelium of the anoderm and the columnar epithelium of the rectum, and uterine cervix cancer that almost always develops in the ‘transformation zone’, an ecotone between the ectocervix (squamous epithelium) and endocervix (columnar epithelium). If the hypothesis is correct, surgically created ecotones should also be prone to cancer development. Indeed, the risk of cancer is increased after uretero-sigmoidostomy, ileal-bladder augmentation, and gastric bypass. The physical and chemical gradients of ecotones disrupt mucosal architecture and expose vulnerable basal cells to carcinogens. The implications of ecotones modifying surgery should be borne in mind during post-operative follow-up and when planning new surgeries. Study of the ecotone concept can elucidate and predict mechanisms in oncology and potentially also in other medical fields.
{"title":"Ecotones—inter-biome transition zones—the wombs of both evolution and cancer","authors":"Ofer N. Gofrit , Tzahi Neuman","doi":"10.1016/j.mehy.2025.111809","DOIUrl":"10.1016/j.mehy.2025.111809","url":null,"abstract":"<div><div>An ecotone is a concept in ecology that refers to a transition zone between two biomes such as forest–grassland. The exposure to environmental gradients induces physiological stress on bordering biotas leading to high genetic diversity, high mutation rate, and intensified selection pressures. We hypothesized that similar forces act on interfaces between epithelia, that these transitions zones can be viewed as ecotones, and that cancer develops in these sites. Examples are: carcinoma of the larynx most commonly developing in the ecotone between the squamous stratified epithelium of the upper glottis and the pseudo-stratified epithelium of the lower glottis, esophageal adenocarcinoma develops in the ecotone between the stratified squamous epithelium of the esophagus and the simple columnar stomach epithelium, anal cancer develops at the ecotone between the squamous stratified epithelium of the anoderm and the columnar epithelium of the rectum, and uterine cervix cancer that almost always develops in the ‘transformation zone’, an ecotone between the ectocervix (squamous epithelium) and endocervix (columnar epithelium). If the hypothesis is correct, surgically created ecotones should also be prone to cancer development. Indeed, the risk of cancer is increased after uretero-sigmoidostomy, ileal-bladder augmentation, and gastric bypass. The physical and chemical gradients of ecotones disrupt mucosal architecture and expose vulnerable basal cells to carcinogens. The implications of ecotones modifying surgery should be borne in mind during post-operative follow-up and when planning new surgeries. Study of the ecotone concept can elucidate and predict mechanisms in oncology and potentially also in other medical fields.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111809"},"PeriodicalIF":0.8,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-02DOI: 10.1016/j.mehy.2025.111810
Sallie S. Schneider , Brian T. Pentecost , Ashley R. Banas , Aliyah Dalier , Vignesh Narayanaswamy , Emma C. Gotschlich , Kathleen F. Arcaro
Chronic inflammation likely contributes to breast cancer risk, but epidemiologic studies are inconclusive. Two types of inflammatory episodes in breast tissue, referred to here as clinical mastitis and subclinical mastitis, have received little to no attention as risk factors for breast cancer. Clinical mastitis represents an acute painful inflammatory state of the breast that in most cases will be quickly treated and resolved. In contrast, subclinical mastitis remains undetected in most cases and may represent chronic inflammation. Based on the concentration of sodium (Na) and cytokines in milk, several publications suggest that subclinical mastitis is relatively common and can persist for extended periods. We propose that subclinical mastitis is a modifiable risk factor for breast cancer. This chronic subclinical inflammatory profile in breast tissue may cause genetic instability and perturb epigenetic mechanisms leading to cancer. We suggest studies to determine the extent that subclinical mastitis is associated with breast cancer risk.
{"title":"Subclinical mastitis during lactation: A modifiable risk factor for breast cancer?","authors":"Sallie S. Schneider , Brian T. Pentecost , Ashley R. Banas , Aliyah Dalier , Vignesh Narayanaswamy , Emma C. Gotschlich , Kathleen F. Arcaro","doi":"10.1016/j.mehy.2025.111810","DOIUrl":"10.1016/j.mehy.2025.111810","url":null,"abstract":"<div><div>Chronic inflammation likely contributes to breast cancer risk, but epidemiologic studies are inconclusive. Two types of inflammatory episodes in breast tissue, referred to here as clinical mastitis and subclinical mastitis, have received little to no attention as risk factors for breast cancer. Clinical mastitis represents an acute painful inflammatory state of the breast that in most cases will be quickly treated and resolved. In contrast, subclinical mastitis remains undetected in most cases and may represent chronic inflammation. Based on the concentration of sodium (Na) and cytokines in milk, several publications suggest that subclinical mastitis is relatively common and can persist for extended periods. We propose that subclinical mastitis is a modifiable risk factor for breast cancer. This chronic subclinical inflammatory profile in breast tissue may cause genetic instability and perturb epigenetic mechanisms leading to cancer. We suggest studies to determine the extent that subclinical mastitis is associated with breast cancer risk.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111810"},"PeriodicalIF":0.8,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.mehy.2025.111807
Isabella Panfoli
Although 90 % of premature babies survive, there is still a need for interventions to improve motor and cognitive neurodevelopmental outcomes. Breast milk is the universally preferred nutrition for the newborn human infant for its numerous benefits. However, premature newborns, especially extremely preterm (below 28 weeks gestational age), do not have access to milk. Those infants often experience severe illness due to the immaturity of multiple systems, needing parenteral nutrition for the first days in the neonatal intensive care unit. Notably, premature breast milk adjusts to the changing needs of the premature for the lactose and protein content. For those babies that cannot be fed maternal milk due to the prematurity of multiple systems, parenteral nutrition is tailored to mimic a pre-birth condition in that it only delivers dextrose as the carbohydrate source. This paper challenges the notion that premature newborns should be considered as though they had not yet been born. It proposes the hypothesis that early supplementation of parenteral nutrition with galactose—emulating the composition of maternal milk—may help mitigate complications associated with premature brain development. Galactose plays a pivotal role in myelination linked to cognitive development. Controlled clinical and animal model trials are proposed to support the hypothesis that the use of breast milk-like parenteral nutrition can prevent neonatal hypoglycemia while improving neurodevelopment in extremely premature newborns.
{"title":"Integration of parenteral nutrition with galactose may improve neurodevelopmental outcomes for preterm newborns","authors":"Isabella Panfoli","doi":"10.1016/j.mehy.2025.111807","DOIUrl":"10.1016/j.mehy.2025.111807","url":null,"abstract":"<div><div>Although 90 % of premature babies survive, there is still a need for interventions to improve motor and cognitive neurodevelopmental outcomes. Breast milk is the universally preferred nutrition for the<!--> <!-->newborn<!--> <!-->human<!--> <!-->infant for its numerous benefits. However, premature newborns, especially extremely preterm (below 28 weeks gestational age), do not have access to milk. Those infants often experience severe illness due to the immaturity of multiple systems, needing parenteral nutrition for the first days in the neonatal intensive care unit. Notably, premature breast milk adjusts to the changing needs of the premature for the lactose and protein content. For those babies that cannot be fed maternal milk due to the prematurity of multiple systems, parenteral nutrition is tailored to mimic a pre-birth condition in that it only delivers dextrose as the carbohydrate source. This paper challenges the notion that premature newborns should be considered as though they had not yet been born. It proposes the hypothesis that early supplementation of parenteral nutrition with galactose—emulating the composition of maternal milk—may help mitigate complications associated with premature brain development. Galactose plays a pivotal role in myelination linked to cognitive development. Controlled clinical and animal model trials are proposed to support the hypothesis that the use of breast milk-like parenteral nutrition can prevent neonatal hypoglycemia while improving neurodevelopment in extremely premature newborns.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111807"},"PeriodicalIF":0.8,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-26DOI: 10.1016/j.mehy.2025.111796
Graeme Greenup
Current models of Parkinson’s disease (PD) emphasize dopaminergic deficits and α-synuclein pathology but struggle to account for its heterogeneous symptoms and progression. This paper proposes PD as a disorder of failed sleep–wake state separation, manifesting as a pathological superposition of REM-like and wake-like brain states. Here, “superposition” refers to the co-presence of incompatible neural programs—REM-associated motor suppression, dream-like cognition, and autonomic dysregulation persisting into wakefulness, and wake-like activity intruding into sleep. This hybrid state disrupts neural boundaries, generating motor and non-motor symptoms through conflicting physiological processes. In humans, sustained cortical overdrive (COD)—high-level cerebral activation that interferes with subcortical sleep–wake circuits—initiates and perpetuates this mixing through a primary vicious circle. A secondary loop involving impaired glymphatic clearance and neuroinflammation accelerates neurodegeneration, which in turn further erodes state boundaries. The model unifies PD symptomatology under a single pathophysiological process, suggests interventions targeting sleep–wake restoration, and offers testable predictions for research with possible extension to other neurodegenerative conditions. It reframes Parkinson’s disease as a measurable, modifiable failure of brain-state regulation—challenging researchers to treat sleep–wake boundary collapse with the same urgency as dopamine loss.
{"title":"Parkinson’s disease as a superposition of wake and sleep states: a hypothesis of vicious cycle neurodegeneration","authors":"Graeme Greenup","doi":"10.1016/j.mehy.2025.111796","DOIUrl":"10.1016/j.mehy.2025.111796","url":null,"abstract":"<div><div>Current models of Parkinson’s disease (PD) emphasize dopaminergic deficits and α-synuclein pathology but struggle to account for its heterogeneous symptoms and progression. This paper proposes PD as a disorder of failed sleep–wake state separation, manifesting as a pathological superposition of REM-like and wake-like brain states. Here, “superposition” refers to the co-presence of incompatible neural programs—REM-associated motor suppression, dream-like cognition, and autonomic dysregulation persisting into wakefulness, and wake-like activity intruding into sleep. This hybrid state disrupts neural boundaries, generating motor and non-motor symptoms through conflicting physiological processes. In humans, sustained cortical overdrive (COD)—high-level cerebral activation that interferes with subcortical sleep–wake circuits—initiates and perpetuates this mixing through a primary vicious circle. A secondary loop involving impaired glymphatic clearance and neuroinflammation accelerates neurodegeneration, which in turn further erodes state boundaries. The model unifies PD symptomatology under a single pathophysiological process, suggests interventions targeting sleep–wake restoration, and offers testable predictions for research with possible extension to other neurodegenerative conditions. It reframes Parkinson’s disease as a measurable, modifiable failure of brain-state regulation—challenging researchers to treat sleep–wake boundary collapse with the same urgency as dopamine loss.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111796"},"PeriodicalIF":0.8,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-26DOI: 10.1016/j.mehy.2025.111797
Yoshito Mukaino , Masahiko Mukaino
While evidence supports the therapeutic effects of acupuncture, particularly for analgesia, the mechanism for its distant effects remains debated. Conventional neurobiological theories, while valid, do not fully account for the rapid, systemic, and meridian-specific responses seen in clinical practice. This paper proposes a ’tension-reset’ hypothesis based on biotensegrity, positing that the interconnected skin-fascia-muscle complex functions as a multilayered tensional network. We hypothesize that acupuncture needling induces a local ’tension reset’ within this complex through mechanisms such as fascial remodeling, altered hyaluronan fluidity, a dermal ’tension switch,’ and neurogenic muscle relaxation. This localized change in mechanical tension is then rapidly propagated throughout the body-wide tensegrity system via mechanotransduction. We propose that these pathways of force transmission are the anatomical correlates of traditional acupuncture meridians. This model is consistent with clinical observations such as reduced tissue stiffness measured by elastography and the clinical efficacy of tension-based diagnostic and treatment approaches. By framing meridians as biomechanical pathways, this tensegrity-based hypothesis offers a testable framework that bridges Eastern medical concepts with Western science, potentially unifying our understanding of acupuncture and other manual therapies while providing a basis for refining clinical techniques.
{"title":"A multilayer ‘tension-reset’ hypothesis: Acupuncture’s distant effects via biotensegrity across skin–fascia–muscle layers","authors":"Yoshito Mukaino , Masahiko Mukaino","doi":"10.1016/j.mehy.2025.111797","DOIUrl":"10.1016/j.mehy.2025.111797","url":null,"abstract":"<div><div>While evidence supports the therapeutic effects of acupuncture, particularly for analgesia, the mechanism for its distant effects remains debated. Conventional neurobiological theories, while valid, do not fully account for the rapid, systemic, and meridian-specific responses seen in clinical practice. This paper proposes a<!--> <!-->’tension-reset’<!--> <!-->hypothesis based on biotensegrity, positing that the interconnected skin-fascia-muscle complex functions as a multilayered tensional network. We hypothesize that acupuncture needling induces a local ’tension reset’ within this complex through mechanisms such as fascial remodeling, altered hyaluronan fluidity, a dermal ’tension switch,’ and neurogenic muscle relaxation. This localized change in mechanical tension is then rapidly propagated throughout the body-wide tensegrity system via mechanotransduction. We propose that these pathways of force transmission are the anatomical correlates of traditional acupuncture meridians. This model is consistent with<!--> <!-->clinical observations such as reduced tissue stiffness measured by elastography and the clinical efficacy of tension-based diagnostic and treatment approaches.<!--> <!-->By framing meridians as biomechanical pathways, this tensegrity-based hypothesis offers a testable framework that bridges Eastern medical concepts with Western science, potentially unifying our understanding of acupuncture and other manual therapies while providing a basis for refining clinical techniques.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111797"},"PeriodicalIF":0.8,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-25DOI: 10.1016/j.mehy.2025.111795
Michał C. Czarnogórski , Layla Settaf-Cherif, Tomasz Drewa, Jan Adamowicz
Despite the unprecedented progress in urological treatment of both benign and malignant bladder conditions, considerable proportion of patients still develop end-stage bladder failure that will eventually require cystectomy. The majority of cystectomies is performed due to bladder cancer. Radical cystectomy with urinary diversion utilizing bowel segments is at present a gold standard, yet it is associated with considerable metabolic complications. With the advent of urinary bladder transplantation research, the new hope emerged for well-informed individuals who would like to preserve natural way of voiding. The vascularized composite bladder allograft transplantation was proven technically and clinically feasible, although for now the indications include only benign bladder conditions, due to the considerable recurrence rate of bladder cancer. We propose hypothetical therapeutic option for non-muscle invasive bladder cancer patients, namely urinary bladder autotransplantation, with blader mucosa decellularization, and subsequent cell seeding with recipients own urothelial progenitor cells. Theoretically, the patient would not require immunosuppressive agents, and would retain natural way of voiding, thus avoiding repeated transurethral bladder tumor resections, BCG instillations, and maintaining high quality of life.
{"title":"Decellularization of urinary bladder autograft in the treatment of bladder cancer","authors":"Michał C. Czarnogórski , Layla Settaf-Cherif, Tomasz Drewa, Jan Adamowicz","doi":"10.1016/j.mehy.2025.111795","DOIUrl":"10.1016/j.mehy.2025.111795","url":null,"abstract":"<div><div>Despite the unprecedented progress in urological treatment of both benign and malignant bladder conditions, considerable proportion of patients still develop end-stage bladder failure that will eventually require cystectomy. The majority of cystectomies is performed due to bladder cancer. Radical cystectomy with urinary diversion utilizing bowel segments is at present a gold standard, yet it is associated with considerable metabolic complications. With the advent of urinary bladder transplantation research, the new hope emerged for well-informed individuals who would like to preserve natural way of voiding. The vascularized composite bladder allograft transplantation was proven technically and clinically feasible, although for now the indications include only benign bladder conditions, due to the considerable recurrence rate of bladder cancer. We propose hypothetical therapeutic option for non-muscle invasive bladder cancer patients, namely urinary bladder autotransplantation, with blader mucosa decellularization, and subsequent cell seeding with recipients own urothelial progenitor cells. Theoretically, the patient would not require immunosuppressive agents, and would retain natural way of voiding, thus avoiding repeated transurethral bladder tumor resections, BCG instillations, and maintaining high quality of life.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111795"},"PeriodicalIF":0.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1016/j.mehy.2025.111793
Yu-Hsiang Lin , Po-Ting Lin , Kuo-Jen Lin , Tzu-Chi Teng , Yu-Ting Chen , Chen-Pang Hou , Jau-Yuan Chen , Chien-Lun Chen
The age-related decline in testosterone, often termed ’andropause,’ is traditionally viewed as an inevitable consequence of aging. However, emerging evidence suggests this decline is more closely associated with accumulating comorbidities than with age itself. We propose a unifying hypothesis of ’sleep disruption-induced hypogonadism,’ an acquired and potentially reversible condition driven by common age-related pathologies such as benign prostatic hyperplasia (BPH), obstructive sleep apnea (OSA), and chronic pain. These conditions precipitate a vicious cycle where symptoms like nocturia cause chronic sleep fragmentation and circadian dysregulation. This, in turn, suppresses the hypothalamic-pituitary–gonadal (HPG) axis, leading to reduced endogenous testosterone. This hypothesis is supported by extensive correlational data linking sleep disorders to low testosterone and, more compellingly, by interventional studies demonstrating that treatment of underlying sleep disruptors—such as BPH surgery or nocturia medication—can significantly restore testosterone levels. This framework also resolves the paradox of why CPAP therapy often fails to raise testosterone by highlighting the powerful confounding role of obesity. The primary implication of this hypothesis is a proposed paradigm shift in clinical practice: from a focus on hormone replacement to a ’sleep-centric,’ cause-oriented approach. We advocate that the diagnostic workup for low testosterone in aging men should include a primary assessment for and treatment of underlying sleep disorders before considering testosterone replacement therapy, fostering a more integrated, multidisciplinary management strategy.
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